Safety and preliminary efficacy trial of BNT142 in patients with CLDN6-positive advanced ovarian, lung, or testicular cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 May 2022 → 22 Dec 2025

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512639-58-00

EudraCT number

2021-005481-18

ClinicalTrials.gov

NCT05262530

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Pharmacokinetic

For Parts 1 and 2: To assess the safety and tolerability of BNT142 at all dose levels tested.

For Part 1: To identify the MAD/MTD/RP2D of BNT142 based on the occurrence of DLTs using the following definitions:
The maximum tolerated dose (MTD) is defined as the highest tolerated dose where less than 1/3 patients experience a dose-limiting toxicity (DLT). The maximum administered dose (MAD) is defined as the highest dose administered, where all dose levels were tolerated during dose escalation.
The Response Evaluation Criteria in Solid Tumors (RP2D) will be defined based on integrated evaluation of safety, tolerability, clinical benefit, Pharmacokinetics, and Pharmacodynamics data from all dose levels tested.

For Part 2: To evaluate the anti-tumor activity of BNT142 according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and for ovarian cancer patients according to definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and cancer antigen-125 (CA) by the Gynecological Cancer Intergroup (GCIG).

Secondary objectives 2

1. For Part 1: To characterize the Pharmacokinetics (PK) profile of the BNT142-encoded protein RiboMab02.1
2. For Parts 1 and 2: To evaluate the anti-tumor activity of BNT142 according to (RECIST) 1.1, and for ovarian cancer patients according to definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and cancer antigen-125 (CA) agreed by the Gynecological Cancer Intergroup (GCIG)

Conditions and MedDRA coding

Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. For both parts: Histological or cytological documentation of a solid tumor that is metastatic or unrespectable provided as a pathology report.
2. CLDN6-positive tumor sample as assessed by central laboratory testing using a Validated immunohistochemistry (IHC) assay (CLAUDENTIFY®6 IHC-Assay) in formalin-fixed paraffin-embedded (FFPE) neoplastic tissues or alternatively from fresh tissue if archival tissue is unavailable
3. Measurable disease per RECIST 1.1 (measurable per RECIST 1.1 or evaluable per GCIG criteria for ovarian tumors).
4. For Part 1 (Dose escalation): Patients with advanced/metastatic ovarian cancer (including fallopian tube and peritoneal), non-squamous non-small cell lung cancer (NSCLC), endometrial, or testicular cancer, for whom there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy, or patients with not otherwise specified (NOS) tumors, rare tumors and cancer of unknown primary (CUP), not included in the predefined eligible tumor types. Patients must have received all available standard therapies, including targeted therapies based on mutation status, and failed at least first line standard of care (SOC) therapy prior to enrollment

Exclusion criteria 9

1. Prior and concomitant therapy: Chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment.
2. Radiotherapy in the last 6 weeks prior to the first dose of BNT142 (excluding brain radiotherapy for which 3 weeks prior to the first dose of BNT142 is allowed).
3. Concurrent systemic (oral or intravenous [IV]) steroid therapy >10 mg prednisone daily or its equivalent for an underlying condition apart from physiologic corticosteroid replacement therapy.
4. Major surgery within 4 weeks before the first dose of BNT142
5. Ongoing or active infection requiring intravenous (IV) treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of BNT142.
6. Prior treatment with a CLDN6 targeting therapy.
7. Side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v.5) Grade ≤1, except for anorexia, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to Grade ≤2. Alopecia of any grade is allowed.
8. Medical conditions Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain metastases may be ligible if they: i. Had radiotherapy, surgery or stereotactic surgery for the brain metastases; ii. Have no neurological symptoms (excluding Grade ≤2 neuropathy); iii. Have stable brain metastasis on the Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) scan within 4 weeks before signing the Informed Consent Form (ICF) iv. Are not undergoing acute corticosteroid therapy or steroid taper.
9. Pregnant or breastfeeding or planning to get pregnant within 6 months of the last dose of BNT142.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to trial treatment.
2. Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs.
3. Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period in the dose escalation.
4. Part 2: Objective response rate (ORR) is defined as the proportion of patients in whom a confirmed complete response (CR) or partial response (PR), per RECIST 1.1, and per GCIG criteria incorporating RECIST 1.1 and CA 125 for the ovarian cancer population is the best overall response

Secondary endpoints 4

1. Pharmacokinetics (PK) parameters including but not limited to area under the concentration-time curve in the dosing interval (AUC), Clearance (CL) and volume of distribution (Vd), Maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration prior to next dose (Ctrough), minimum observed concentration (Cmin), and half-life (t½).
2. Objective response rate (ORR) (Part 1 only) is defined as the proportion of patients in whom a confirmed CR or PR, per RECIST 1.1, is the best overall response
3. Disease control rate (DCR) is defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1 [and per GCIG criteria for ovarian cancer patients], SD assessed at least 6 weeks after first dose) as best overall response.
4. Duration of response (DOR) is defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST 1.1) or death from any cause, whichever occurs first.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 10

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications